The long-term goal of this program is to determine the importance of the activation of circulating pancreatic proelastase 2 by specific plasma activators in the pathogenesis of degenerative elastic tissue changes observed in emphysema, atherosclerosis, and aging. In order to accomplish this goal, the following specific objectives are proposed: 1. To demonstrate the production of active elastase 2 from the activation of proelastase 2 by plasma enzymes. Accomplishment of this goal will necessitate the development of techniques for enzymatic determination of elastase 2 in the presence of plasma protease inhibitors. 2. To isolate, purify, and characterize the plasma proelastase 2 activator(s) as follows: a) The parameters and kinetics of activation of proelastase 2; b) Inhibition by chemical and biological inhibitors; and c) The specificity of the activator(s) for human pancreatic proelastase 2. 3. To develop a specific radioimmunoassay for the proelastase 2 activator (s). The assay will be employed to determine the possible age variation of plasma proelastase 2 activator (s) levels from normal individuals of various ages. The levels of activator (s) will then be determined in sera of patients with emphysema and from atherosclerosis patients.